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本文采用超高效液相色谱质谱联用(UPLC-MS)胆汁酸代谢网络分析方法评价黄药子乙醇提取物(ethanol extraction,ET)和单体化合物黄独素B(diosbulbin B,DB)致小鼠的肝毒性。通过小鼠毒性实验,ET和DB给药组小鼠都可见明显的肝脏毒性。血清胆汁酸含量测定结果经主成分分析后,空白组和给药组区分明显,ET和DB给药组矢量方向一致,但两者之间也有一定距离,提示DB是黄药子致肝毒性的主要毒性成分之一。经偏最小二乘法-判别分析后,结果表明牛磺酸结合型胆汁酸对表征ET和DB致小鼠肝毒性具有重要的贡献,且以牛磺酸结合型为主的胆汁酸与ALT和AST具有很好的相关性,因此以牛磺酸结合型为主的胆汁酸可作为评价黄药子致小鼠肝毒性的生物标识物。本研究为进一步深入评价黄药子致肝毒性及致毒机制研究奠定了基础。
In this paper, UPLC-MS analysis of bile acid metabolism was used to evaluate the hepatotoxicity in mice induced by ethyl alcohol extraction (ET) and monomer compound diosbulbin B . Through the mouse toxicity test, ET and DB administration group mice showed obvious liver toxicity. The results of serum bile acid determination by principal component analysis, the blank group and the treatment group were significantly different, ET and DB administration group vector direction, but there is a certain distance between the two, suggesting that DB is the main toxicity of xanthium-induced hepatotoxicity One of the ingredients. After partial least-squares-discriminant analysis, the results showed that taurine-conjugated bile acids have an important contribution to the characterization of hepatotoxicity in mice induced by ET and DB. Taurine-binding bile acids and ALT and AST Has a good correlation, so taurine-based bile acids can be used as a biomarker to evaluate xanthate-induced hepatotoxicity in mice. This study lays the foundation for the further in-depth evaluation of the hepatotoxicity induced by Xanthium sibiricum and its mechanism of toxicity.